Background: The endobronchial diagnosis of peripheral lung lesions suspected of lung cancer remains a challenge from a navigation as well as an adequate tissue sampling perspective. Cone-beam computed tomography (CBCT) guidance is a relatively new technology and allows for 3-dimensional imaging confirmation as well as navigation and biopsy guidance, but, also involves radiation. This study investigates how radiation exposure and diagnostic accuracy in the CBCT-guided navigation bronchoscopy evolves with increasing experience, and, with a specific tailoring of CBCT and fluoroscopic imaging protocols towards the procedure. Patients and Methods: In this observational clinical trial, all 238 consecutive patients undergoing a CBCT-guided navigation bronchoscopy from the start of our CBCT-guided navigation bronchoscopy program (December 2017) until June 2020 were included. Procedural dose characteristics and diagnostic accuracy are reported as a function of time. Results: Procedural radiation exposure as measured by the dose area product initially was 47.5 Gy·cm² (effective dose: 14.3 mSv) and gradually reduced to 25.4 Gy·cm² (5.8 mSv). The reduction in fluoroscopic dose area product was highest, from 19.0 Gy·cm² (5.2 mSv) to 2.2 Gy·cm² (0.37 mSv, 88% reduction), despite a significant increase of fluoroscopy time. The diagnostic accuracy of navigation bronchoscopy increased from 72% to 90%. Conclusion: A significant learning effect can be seen in the radiation safety and diagnostic accuracy of a CBCT-guided and augmented fluoroscopy–guided navigation bronchoscopy. With increasing experience and tailoring of imaging protocols to the procedure, the procedural accuracy improved, while the effective dose for patients and staff was reduced.

Lymph node staging in patients with non-small cell lung cancer is crucial for determining prognosis and treatment. Our objective was to evaluate the clinical- to pathological agreement of guideline-concordant nodal staging in patients with resectable NSCLC and assess occurrence and distribution of occult lymph node metastases (OLM). In a retrospective single center cohort study (n = 390), we analyzed all surgically treated NSCLC patients from January 2015 until April 2019. Patients were classified into sub-groups (1) mediastinal staging by PET-CT/CT-scan (IMAGE-group) or (2) invasive staging by endobronchial ultrasound and mediastinoscopy (INVAS-group). Agreement between final clinical (cN) and pathological nodal stage (pN) and the presence and location of OLM are analyzed. Agreement between cN- and pN-stage was 86.3 % in the IMAGE-group (n = 117) and 50.9 % in the INVAS-group (n = 167). Occult N1 disease was found in 33 patients (16.6 % in cN0) of which 52 % occurred in LN-regions 12-14. Occult N2 disease was found in 20 cases (6.5 % in cN0 and 12.7 % in cN1). Combined, 23.1 % of all pre-operatively cN0-staged patients (n = 46/199) had OLM (pN+), of which 12.1 % (24/199) had metastases in regions 5-6 and/or 12-14. Of all patients with OLM, 50.0 % (23/46) had primary tumors ≤30 mm. OLM are frequently identified in clinically N0/N1 NSCLC, also in tumors <3 cm, and often in regions beyond reach of current staging techniques. These findings should be addressed when non-surgical treatment or sub-lobar resections are considered for early stage lung cancer.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology are rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimize radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

Background: In lung cancer staging, mediastinal lymph nodes are currently aspirated using endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) based on size and FDG-PET avidity. EBUS strain elastography (SE) is a new technique that may help predict the presence of malignancy. However, a standardized assessment strategy for EBUS-SE measurement is lacking. Objectives: The aim of this study was to determine the optimal assessment strategy for investigating the predictive value of EBUS-SE in mediastinal lymph nodes. Methods: Two qualitative visual analogue scale strain scores and two semiquantitative strain elastography measurements (a strain histogram and strain ratio) were acquired in 120 lymph nodes of 63 patients with (suspected) lung cancer. The dataset was randomized into an 80% training dataset to determine cut-off values. Performance was consecutively tested on the remaining 20% and the overall dataset. Results: The semiquantitative mean histogram scoring strategy with a cut-off value of 78 (range 0–255) showed the best and most reproducible performance in prediction of malignancy with 93% overall sensitivity, 75% specificity, 69% positive predictive value, 95% negative predictive value, and 82% accuracy. Combining the EBUS-SE mean histogram scoring outcome with PET-CT information increased the post-test probability of disease in relevant clinical scenarios, having a positive test likelihood ratio of 4.16 (95% CI 2.98–8.13) and a negative test likelihood ratio of 0.14 (95% CI 0.04–2.81) in suspicious lymph nodes based on FDG-PET or CT imaging. Conclusions: EBUS-SE can potentially help predict lymph node malignancy in patients with lung cancer. The best semiquantitative assessment method is the mean strain histogram technique.

Background: Systematic assessment of lymph node status by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is indicated in (suspected) lung cancer. Sampling is herein guided by nodal size and FDG-PET characteristics. Ultrasound strain elastography (SE) might further improve risk stratification. By imaging tissue deformation over time, SE computes relative tissue strain. In several tissues, a lower strain (deformation) has been associated with a higher likelihood of malignancy. Objectives: To assess if EBUS-SE can independently help predict malignancy, and when combined with size and FDG uptake information. Methods: This multicenter (n = 5 centers) prospective trial included patients with suspected or proven lung cancer using a standardized measurement protocol. Cytopathology combined with surgery or follow-up imaging (>6 months) were used as reference standard. Results: Between June 2016 and July 2018, 327 patients and 525 lymph nodes were included (mean size 12.3 mm, malignancy prevalence 0.48). EBUS-SE had an overall AUC of 0.77. A mean strain <115 (range 0–255) showed 90% sensitivity, 43% specificity, 60% positive predictive value, and 82% negative predictive value. Combining EBUS-SE (<115) with size (<8 mm) and FDG-PET information into a risk stratification algorithm increased the accuracy. Combining size and SE showed that the 48% a priori chance of malignancy changed to 11 and 70% in double negative or positive nodes, respectively. In the subset where FDG-PET was available (n = 370), triple negative and positive nodes went from a 42% a priori chance of malignancy to 9 and 73%, respectively. Conclusions: EBUS-SE can help predict lymph node malignancy and may be useful for risk stratification when combined with size and PET information.

Objectives To determine if cone beam CT-guided navigation bronchoscopy (CBCT-NB) is a cost-effective diagnostic procedure in patients with a pulmonary nodule (PN) with an intermediate risk for lung cancer. Materials and methods Two decision analytical models were developed to compare the long-term costs, survival and quality of life. In the first model, CBCT-NB was compared with CT-guided transthoracic needle biopsy (TTNB) in TTNB eligible patients. In the second model, CBCT-NB was compared with direct treatment (without pathology proven lung cancer) in patients for whom TTNB is not suitable. Input data were gathered in-house, from literature and expert opinion. Effects were expressed in quality-adjusted life years (QALYs). Sensitivity analyses were used to assess uncertainty. Results CBCT-NB can be cost-effective in TTNB eligible patients with an incremental cost-effectiveness ratio of €18 416 in an expert setting. The probabilistic sensitivity analysis showed that in 69% and 90% of iterations CBCT-NB remained cost-effective assuming a willingness to pay (WTP) of €20 000 and €80 000 per QALY. CBCT-NB dominated in the treatment strategy in which TTNB is not suitable. The probabilistic sensitivity analysis showed that in 95% of iterations CBCT-NB remained the dominant strategy, and CBCT-NB remained cost-effective in 100% of iterations assuming a WTP limit of €20 000. In the comparison between CBCT NB and TTNB, the deterministic sensitivity analysis showed that the diagnostic properties and costs of both procedures have a large impact on the outcome. Conclusions CBCT-NB seems a cost-effective procedure when compared with TTNB and when compared with a direct treatment strategy in patients with an intermediate risk PN.